This report describes spastic paraplegia 20 (SPG20), which is a subtype of spastic paraplegia; SPG20 exhibits autosomal recessive inheritance. This disease is commonly called Troyer syndrome. The human gene implicated in this disease is SPART (Spartin), which encodes a protein containing a MIT (microtubule interacting and trafficking) domain, and is implicated in regulating endosomal trafficking and mitochondria function. There is a single fly ortholog, spartin, for which a classical amorphic allele and RNAi-targeting constructs have been generated.
A UAS construct of the wild-type human gene, Hsap\SPART, has been introduced into flies. Heterologous rescue (functional complementation) has been demonstrated: pan-neuronal expression of this construct rescues larval and adult phenotypes observed for Dmel\spartin mutants.
Animals carrying an amorphic mutation of Dmel\spartin are viable and fertile; observed phenotypes include aspects relevant to spastic paraplegia, such as neuroanatomy defective and locomotor behavior defective. Histological assays using the mutations of the fly gene have allowed characterization of genetic interactions. Physical interaction(s) of the Dmel\spartin protein product have been described; see below and in the gene report for spartin.
[updated Jan 2017 by FlyBase; FBrf0222196]
The hereditary spastic paraplegias (SPG, HSP) are a large group of clinically and genetically diverse disorders characterized by progressive, usually severe, lower extremity spasticity and weakness. SPG is classified by mode of inheritance (autosomal dominant, autosomal recessive, and X-linked) and whether the primary symptoms occur in isolation ('uncomplicated SPG') or with other neurologic abnormalities ('complicated SPG'). [from OMIM:182600; 15.06.29]
[SPASTIC PARAPLEGIA 20, AUTOSOMAL RECESSIVE; SPG20](https://omim.org/entry/275900)
The most common characteristics of SPG20 (Troyer syndrome) are spasticity of the leg muscles, progressive muscle weakness, paraplegia, muscle wasting in the hands and feet (distal amyotrophy), small stature, developmental delay, learning disorders, speech difficulties (dysarthria), and mood swings. [from Genetics Home Reference, GHR_condition:troyer-syndrome, 2015.07.01]
SPG20 (Troyer syndrome) is inherited as an autosomal recessive; it is caused by mutations in the gene SPG20 (spartin). Most described cases are from the Old Order Amish population of Ohio. [from OMIM:275900; 15.07.01]
This form of spastic paraplegia has been reported to occur in two large kindreds, an Amish kindred in the United States and an Arab kindred in Oman. [from NORD: Hereditary Spastic Paraplegia; 2016.09.02]
SPG20 encodes a protein consisting of an N-terminal MIT (contained in microtubule-interacting and trafficking molecules) domain, a central Eps15-interacting domain, and a C-terminal senescence domain (Ciccarelli et al., 2003, pubmed:12676568; Bakowska et al., 2005, pubmed:16036216).
The SPG20 (spartin) gene shares sequence similarity with the N-terminal region of spastin (SPAST, causative gene of SPG4), as well as with other proteins involved in the morphology and membrane trafficking of endosomes; it has effects upon microtubule dynamics. [from OMIM:607111; 15.07.01]